PMID: 11920750Mar 29, 2002Paper

A physicochemical basis for the extensive intestinal lymphatic transport of a poorly lipid soluble antimalarial, halofantrine hydrochloride, after postprandial administration to dogs

Journal of Pharmaceutical Sciences
Shui-Mei KhooWilliam N Charman

Abstract

The highly lipid soluble, free-base form of halofantrine (Hf base; approximately 50 mg/mL in triglyceride lipids), a highly lipophilic (calculated log P approximately 8.5) antimalarial, has recently been shown to undergo significant intestinal lymphatic transport (54% of administered dose) after postprandial administration to dogs. In contrast, the clinically available hydrochloride salt of Hf (Hf small middle dot HCl), was not considered to be a likely substrate for lymphatic transport because its solubility in long-chain triglyceride lipids is low (< 1 mg/mL). This paper reports the lymphatic transport of Hf after postprandial administration of Hf.HCl, which was surprisingly high at 47% of the administered dose, and not significantly different from that of Hf base. It was postulated that partial conversion of solubilized Hf.HCl to the highly lipid soluble Hf base within the intestinal lumen might account for the extensive lymphatic transport. However, as Hf is a tertiary amine with an expected pK(a) of > 10, at gastrointestinal pH, the fraction of Hf present as the free base form is likely to be extremely low. Physicochemical studies exploring the solubility and pK(a) of Hf suggest that Hf.HCl was extensively solubilized foll...Continue Reading

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Citations

Sep 19, 2003·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·René HolmWilliam N Charman
Nov 7, 2003·Journal of Pharmaceutical Sciences·Agnes Taillardat-BertschingerWilliam N Charman
Jun 22, 2011·Advanced Drug Delivery Reviews·Jaime A YáñezKevin B Alton
Jul 10, 2007·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·S StegemannH Lindén
Mar 19, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Erik SjögrenPeter Langguth
Jun 10, 2009·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Subhashis ChakrabortySanjay Singh
Mar 29, 2013·International Journal of Pharmaceutics·Harshad SheteVandana Patravale
Aug 18, 2016·Molecular Pharmaceutics·P J SasseneA Müllertz
Dec 29, 2020·Journal of Pharmaceutical Sciences·Michael J DoltonYuan Chen
Dec 6, 2012·Journal of Agricultural and Food Chemistry·Yung-Jen Tsai, Tung-Hu Tsai

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